The effects of aging and age-related macular degeneration on photoreceptor function and the supporting retinal pigment epithelial cells is the focus of this proposal. The extent of structural and functional damage across retinal area within retinal and subretinal layers will be probed. We will test the hypothesis that accumulation of subretinaI deposits leads to loss of photoreceptor function. In this context we have two long-term goals: first, to provide a better definition of what is normal aging, as opposed to early signs of disease; second, to understand the role of disease in the death of photoreceptors, including subretinal pathology such as deposits, new vessel membranes, and presence of fluid in detachment. We will determine which portions of the retina are damaged by apparently well-localized vs. diffuse retinal disease processes. This information can be of use for evaluating possible preventative measures, determining the focal effects of treatment, estimating prognosis, and understanding disease processes. To compare structure with function, we use a research Scanning Laser Ophthalmoscope (SLO). To quantify subretinal pathologies we use infra-red imaging to quantify the size and location of sub-retinal features such as deposits, fluid accumulation, and sub-retinal vessels, even through cataract and hemorrhage. To quantify the composition of subretinal pathology, seen with infra-red imaging, and verify its position, we use fluorescein angiography. The location of potential damage to photoreceptors from deposited or exudative material is quantified. The composition of the subretinal pathology will be probed by the pattern of fluorescent binding. To assess the structural integrity of the central cones, their ability to direct light will be quantified with a reflectometric Stiles-Crawford I measurement. To quantify photopigment function, foveal cone and peripheral rod photopigment distribution are measured. Our retinal densitometry measurements are rapid and resistant to stray light. Visual sensitivity at selected retinal loci will be measured with increment threshold. These will be compared with predicted amounts of sensitivity loss from loci of structural damage and amount of photopigment present. Cross sectional studies of clinically normal adults quantify the a) subretinal changes and b) pattern across the retina of photoreceptor loss with aging and in groups at risk for age-related macular degeneration. A statistical definition of normal will be developed for early detection of age-related macular degeneration. We will compare the photopigment loss and structural changes in early and exudative disease in a cross-sectional study and how they are affected by hypertension.